tbuckley/cabot-search huggingface dataset:
Elucidation of the mechanisms of trastuzumab-induced severe cardiotoxicity using patient-derived iPSCs cardiomyocyte model.
Authors: Ritsuko Sasaki, Nagomi Kurebayashi, Hidetaka Eguchi, Yoshiya Horimoto, Takahiro Shiga, Sakiko Miyazaki, Taku Kashiyama, Wado Akamatsu, Mitsue Saito
Journal: Journal of Clinical Oncology (2022)

e24065 Background: Trastuzumab (Tmab) is a highly effective anticancer drug, but it is associated with unpredictable and non-accumulative cardiotoxicity, which can interfere with continuous treatment. In order to elucidate the mechanism of Tmab-induced cardiotoxicity, we attempted to reproduce the cardiotoxicity using disease-specific iPS cells from patients who had suffered myocardial dysfunction after Tmab administration. Methods: From 468 breast cancer patients treated with Tmab at our hospital, we selected three patients exhibiting severe cardiotoxicity (SP) with left ventricular ejection fraction reduced by more than 30% from baseline, and three non-cardiotoxic patients (NP)matched with the SP group on various clinical factors. Patient-specific iPSCs established from peripheral blood samples were differentiated to cardiomyocytes (iPSC-CMs). We evaluated contractility and intracellular metabolic function. Results: Treatment of iPSC-CMs with Tmab for 7 days reduced contraction and relaxation velocity, which were more evident in SP than in NP ( p= .032, .044, respectively). In addition, SP-iPSC-CMs showed a significant decrease in ATP ( p= .048), increase in reactive oxygen species production ( p= .046), and increase in autophagy activity ( p= .030) compared to NP-iPSC-CMs. In contrast, there was no significant difference in the suppression of mitochondrial maximal respiratory rate by Tmab between the two groups. Conclusions: We demonstrated that iPSC-CMs well recapitulate the individual differences in contractile and intracellular metabolic dysfunction caused by Tmab.
NFB-06. Laser Interstitial Thermal Therapy as a Radiation-Sparing Approach for Children with Cancer Predisposition
Authors: Sergio Guadix, Neranjan de Silva, Mark Souweidane
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Li-Fraumeni (LFS) syndrome confers a predisposition for the formation of a broad range of tumors. Estimates of post-radiation secondary malignancy in the context of LFS cohorts range from 20-50%. Therefore, alternative therapeutic strategies are prioritized. Laser interstitial thermal therapy (LITT) is a minimally invasive technique utilizing thermal ablation for tumor control that is not associated with any ionizing radiation or known mutagenic effect. We describe the case of a child with LFS previously treated for CPC who developed a secondary low-grade glial neoplasm of the brain treated safely with MR-guided LITT as part of a radiation-sparing therapeutic approach. METHODS: Retrospective chart review identified a patient with recurrent CPC associated with LFS who was treated with LITT for a secondary low-grade glial tumor. A descriptive report is provided, including a review of clinical and radiologic outcomes of the procedure. RESULTS: A 4-year-old male with left parietal WHO Grade III CPC associated with a TP53 germline mutation met inclusion criteria. The patient underwent neoadjuvant platinum-based chemotherapy before near-total resection, followed by immunotherapy with 131I-8H9 and 30 fractions of 54Gy total proton therapy. He remained without evidence of disease for two years prior to developing a slow-growing mass adjacent to the left frontal horn. This lesion demonstrated radiographic progression on neuroimaging and was deemed to be a poor candidate for surgical removal. Stereotactic biopsy revealed a low-grade glial neoplasm staining positive for GFAP and Olig2. MR-guided LITT was concurrently performed for ablative therapy of the lesion without complication. Greater than 8-month follow-up has revealed no subsequent disease. CONCLUSIONS: Alternatives to ionizing radiation for brain tumors should be explored for patients with cancer predisposition, such as LFS. Long-term follow up will be needed to ensure local disease control and avoidance of treatment-related neoplasms.
Diagnostic Excellence and Patient Safety
Authors: Nirav R. Shah, Tejal K. Gandhi, David W. Bates
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The update from Bladder Cancer Italian Active Surveillance (BIAS) project for low-grade bladder tumors: Long-term oncological outcomes of patients under active surveillance
Authors: E. Beatrici, R. Contieri, N. Frego, V. Fasulo, P. Diana, M. Paciotti, C. Saitta, G. Chiarelli, P. Arena, A. Gobbo, P.P. Avolio, A. Uleri, N.M. Buffi, M. Lazzeri, P. Casale, A. Saita, G. Guazzoni, G. Lughezzani, R. Hurle
Journal: European Urology (2022)
Utilization of telemedicine among patients newly diagnosed with cancer.
Authors: I-Wen Pan, Tina W.F. Yen, Ya-Chen Tina Shih
Journal: Journal of Clinical Oncology (2022)

1595 Background: The use of telemedicine among cancer patients remains limited. Because of the COVID-19 pandemic, CMS expansion of telehealth with 1135 waiver was enacted in March 2020, broadening the opportunities to provide patient care using telemedicine. This study examined the impact of the CMS expansion on the use of telemedicine among cancer patients. Methods: We identified newly diagnosed patients with 5 common cancers (breast, prostate, lung, colorectal, and lymphoma) between 3/2019 and 12/2020 from Optum’s de-identified Clinformatics Data Mart Database. Patients who had 6 months of full enrollment (3 months before and 3 months after the first [index] cancer diagnosis date), had cancer claims on 3 separate dates within 3 months of the index date for the specific cancer diagnosis, and no prior history of cancer were included. We defined telemedicine use as patients who had a telemedicine procedure code within 1 month of their index diagnosis and had the cancer diagnosis on the telemedicine claim. We conducted an interrupted time series analysis to examine the impact of CMS expansion on telemedicine use. A multivariable logistic regression model was used to identify factors associated with telemedicine use during the post-expansion period. Results: Of 96,632 patients included, the average crude rate of telemedicine use was 0.12% before and 14.2% after the expansion in March 2020 (see Table). There was a significant impact of expansion on telemedicine use (21% increase; p&lt;0.001). The peak rate (adjusted) was 28% in April 2020, decreasing and plateauing in July/August 2020, with rates staying in the range of 10-12% between August and December 2020. During the post-expansion period, lymphoma, prostate, and lung cancer patients (adjusted rates: 14.6%, 15.7%, and 15.9%, respectively) were more likely to use telemedicine compared to patients who had breast (12.7%) or colorectal (12.3%) cancer. Patients who were older (adjusted rates: ≥65 years, 13.8%; 50-64, 14.2%; 20-49, 18.6%), Black (12.4% vs 14.4% for White, 15.5% for Hispanic and 16.6% for Asian), resided in East South Central census division (8.4% vs 23.5% in New England) and had Medicare (12.2% vs 20.3% for commercial insurance) were less likely to use telemedicine (all p&lt;.001). Conclusions: After the CMS telehealth expansion, the use of telemedicine among newly diagnosed cancer patients increased significantly. Telemedicine use varied by patient age, geographic location, race/ethnicity, and payer. Further research is needed to understand the pattern of telemedicine use.[Table: see text]
Endothelial ACKR3 drives atherosclerosis by promoting immune cell adhesion to vascular endothelium
Authors: E Van Der Vorst, S Gencer, Y Jansen, S Bayasgalan, Y Yan, M Bianchini, I Cimen, M Mueller, L Peters, R Megens, J Duchene, P Lemnitzer, O Soehnlein, C Weber, Y Doering
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Deutsche Forschungsgemeinschaft SFB1123 European Research Council AdG_692511 Background Genome wide association studies revealed a strong association between the CXCL12 gene locus and cardiovascular diseases, highlighting its receptors CXCR4 and atypical chemokine receptor-3 (ACKR3) as targets for CVD research. Although vascular CXCR4 is well studied in atherosclerosis, the exact role of ACKR3 remains elusive. Therefore, the aim of this project is to decipher the role of vascular ACKR3 in atherosclerosis. Methods Vascular endothelium (Bmx-cre) specific Ackr3 deficient mice on Apoe-/- background were fed with a cholesterol-rich diet. Lesions in the aortic roots and arches were analyzed via H&amp;E staining. The phenotype was further characterized employing ex-vivo perfusion and intravital microscopy for cell adhesion and Evans-blue injection for endothelial permeability. Signaling studies are performed in human coronary artery endothelial cells (HCAECs). Results Endothelial Ackr3 deficiency resulted in significantly smaller atherosclerotic lesions, accompanied by a more stable plaque phenotypes (more lesional collagen and smooth muscle cell content, smaller necrotic cores). Endothelial-Ackr3-/- mice revealed a reduction in plaque macrophage content and ICAM positive endothelial cells in atherosclerotic lesions. Moreover, immune cell adhesion on carotid arteries lacking endothelial ACKR3 was decreased whilst endothelial permeability was not affected. ACKR3 silencing in TNF-stimulated HCAECs decreased adhesion molecule expression and downregulated MAPK signaling and NF-kB p65 phosphorylation. Endothelial cells in atherosclerotic lesions also revealed decreased phospho-NF-kB p65 expression in Ackr3 deficient mice. Conclusion Collectively, our findings indicate that arterial endothelial ACKR3 fuels atherosclerosis by mediating endothelium-immune cell adhesion, most likely through inflammatory MAPK and NF-kB pathways resulting in increased adhesion molecule expression.
GCT-19. Toward understanding of the pathogenesis of central nervous system germ cell tumors
Authors: Koichi Ichimura, Hirokazu Takami, Kaishi Satomi, Yuko Matsushita, Keita Terashima, Ryo Nishikawa
Journal: Neuro-Oncology (2022)

Abstract Central nervous system germ cell tumors (CNSGCT) are the most enigmatic brain tumors that arise predominantly in children and young adults. CNSGCTs are rare in Europe and North America, while they are rather common in East Asia. The genetic basis of the distinct regional prevalence is yet to be elucidated. The WHO Classification of Central Nervous System Tumours recognizes 6 subtypes of CNSGCT, however multiple subtypes are often present as a mixed tumor, and the subtype may change at the recurrence. In 2012, we organized the Intracranial Germ Cell Tumor Genome Analysis Consortium of Japan (iGCT Consortium) and have collected nearly 300 frozen tumor specimen and patients’ information for CNSGCT cases since then to comprehensively investigate the genomic/epigenomic mechanism of CNSGCT development. We found that alterations of the MAPK and/or PI3K pathways were present in approximately 50% of all subtypes of CNSGCTs, KIT mutations being the most common. Germinomas are characterized by global hypomethylation, indicating that their cell of origin may be primordial germ cells. Transcriptomic profiling suggested that germinomas and non-germinomatous germ cell tumors (NGGCTs) developed from the common cell of origin and then diverted at some stage. We also showed that components of mixed CNSGCT shared the identical somatic mutation while having distinct methylation profiles, supporting the common cell-of-origin theory. In this paper, we will present an overview of our investigation in the iGCT Consortium as well as some of the ongoing projects, single cell RNA sequencing among others.
LGG-26. Predicting MAPK inhibitor sensitivity in pediatric low-grade gliomas with novel gene expression-derived signatures
Authors: Romain Sigaud, Caroline Heß, Thomas Hielscher, Nadine Winkler, Florian Selt, Daniela Kocher, Leo Nonnenbroich, Diren Usta, Alex Sommerkamp, Isabel Büdenbender, David Capper, Ulrich W Thomale, Pablo Hernáiz Driever, Michè le Simon, Arend Koch, Nada Jabado, Augusto F Andrade, Netteke Schouten- van Meeteren, Eelco Hoving, Cornelis M van Tilburg, Stefan M Pfister, Olaf Witt, David T W Jones, Till Milde
Journal: Neuro-Oncology (2022)

Abstract Pediatric low-grade glioma (pLGG), the most common brain tumors in children, are driven by alterations in the MAPK pathway. Several clinical trials have shown the potential for MAPK inhibitor (MAPKi) treatment in pLGG. However, the range of response to MAPKi is heterogeneous, even between tumors sharing the same driving MAPK alteration. A predictive stratification tool is needed to identify tumors that will be sensitive to MAPK inhibition. We generated sensitivity gene signatures for each MAPKi class (BRAFi, MEKi, ERKi), based on MAPK-related genes differentially regulated between MAPKi sensitive and non-sensitive cell lines from the Genomics of Drug Sensitivity in Cancer (GDSC) dataset. Single sample Gene Set Enrichment Analysis was used to measure and validate the MAPKi predictive sensitivity scores in the GDSC dataset and an independent patient-derived xenograft (PDX) dataset (XevaDB). The validated signatures were tested in a pLGG-specific background, using gene expression data from pLGG cell lines and primary pLGG samples. Our MAPKi sensitivity signatures discriminated MAPKi sensitive and non-sensitive cells in the GDSC dataset, and significantly correlated with MAPKi response in the PDX dataset. The sensitivity scores discerned gliomas with varying MAPK alterations from those without MAPK alterations, and showed higher scores in pLGG compared to high-grade gliomas and normal brain tissue. MAPKi-predicted sensitivity was heterogeneous within pLGG groups with a common MAPK alteration, as observed in MAPKi clinical trials. Intriguingly, we observed a strong positive correlation between our MAPKi sensitivity signature scores and the predicted immune cell infiltration rate as determined by the ESTIMATE score. These data demonstrate the potential relevance of gene-expression signatures to predict response to MAPKi treatment in pLGG patients, worth of further investigation in a prospective manner in upcoming clinical trials. In addition, our data could support a role of immune cell infiltration in the response to MAPKi in pLGG, warranting further validation.
Re: Amar U. Kishan, Xiaoyan Wang, Yilun Sun, et al. High-dose Radiotherapy or Androgen Deprivation Therapy (HEAT) as Treatment Intensification for Localized Prostate Cancer: An Individual Patient–data Network Meta-analysis from the MARCAP Consortium. Eur Urol. 2022;82:106–14
Authors: Yongfeng Lao, Yanan Wang, Zhilong Dong
Journal: European Urology (2022)
Sutureless purely off-clamp robot-assisted partial nephrectomy: Nuclear renal scan findings from a pilot study
Authors: A. Brassetti, S. D'Annunzio, U. Anceschi, A. Bove, M.C. Ferriero, S. Guaglianone, R. Mastroianni, L. Misuraca, G. Tuderti, C. De Nunzio, G. Simone
Journal: European Urology (2022)
Breast cancer characteristics and time to chemotherapy initiation in Belize.
Authors: Wayne Wong, James Dickerson, Rupali Sood, Ramon Argenes Yacab, Yannis Valtis, John Lattin, Philip Garrity, Ami Siddharth Bhatt, Franklin W. Huang
Journal: Journal of Clinical Oncology (2022)

e18643 Background: Breast cancer is the most common cancer in low and middle-income countries. Belize, a middle-income country in the Caribbean with significant inequality, lacks a national screening program and has limited treatment capacity. There are no studies describing breast cancer characteristics in Belize in the available literature. We collected data from the sole public oncology clinic in the country, established in 2018 at Karl Heusner Memorial Hospital (KHMH), to describe the characteristics of breast cancer patients and establish baseline measurements of time to chemotherapy initiation for the curative intent treatment population; the aim being to identify potential areas for quality improvement. Methods: We performed a retrospective chart review of available patient data from December 2020 to December 2021. We examined the time from a patient’s initial visit at KHMH until chemotherapy initiation (TCI) in the neoadjuvant setting with patients stratified by stage. Significant outliers (predominantly patients with misclassified data or those with private access to physicians and therapeutics) were excluded. Results: The clinic provided care for 80 patients with biopsy-proven breast cancer between December 2020 to December 2021. Patients were 97% female with a median age of 55 (Range: 34-81). For stageable patients (n=75), 33% presented with clinically localized disease, 49% with locally advanced, and 17% with recurrent or metastatic disease. Of the 51 patients on chemotherapy, 57% were receiving preoperative treatment, 31% were on adjuvant therapy, and 12% on palliative therapy. Patients not on therapy (n=29) at KHMH were either in surveillance, referred to a private cancer center, or deceased. Neoadjuvant TCI was calculated for 21 patients after the removal of outliers (n=5). The majority of these patients arrived at their initial clinic visit with a biopsy-proven diagnosis. Mean TCI for early stage disease was 49 days (n=7, 95% CI [9, 89]) and locally advanced disease was 36 days (n=14, 95% CI [12, 61]). Aggregate mean TCI was 40 days (n=21, 95% CI [19, 62]). Conclusions: In Belize, breast cancer affects younger women and patients present with later stages of disease than in high-income countries; however, time to chemotherapy initiation in a small sample of neoadjuvant patients at the Belizean clinic was comparable. Given the inherent limitations of small samples of data, additional investigation is needed to support these findings, as well as to delineate patient barriers to access and potential for improvements in clinic follow-up. Nevertheless, indications of a robust TCI call for further characterization of this newly established cancer clinic and its practices.
Sealing the leak: A 10-year multicentre experience managing refractory post retroperitoneal lymph node dissection chylous ascites
Authors: J. O'Brien, T.G. Manning, B. Kelly, K. Chen, D. Merrilees, J. Joseph, S. Sengupta, J. Goad, D. Bolton, N. Lawrenstchuk
Journal: European Urology (2022)
Comparison of maintenance of intravesical BCG therapy between 1 year and more than 1 year therapies for recurrence rate in high-risk NMIBC: Systematic review and network meta-analysis according to EAU COVID-19 recommendation
Authors: Y.J. Moon, J.Y. Jeong, D.Y. Chung, A.J. Almujalhem, A.A. Alqahtani, M.A. Alkhureeb, H.H. Han, D.H. Kang, H.D. Jung, K.S. Cho, J.Y. Lee
Journal: European Urology (2022)
Relevance of necroptosis in the hearts subjected to acute versus chronic ischemia/reperfusion injury
Authors: C Horvath, A Szobi, M Young, I Jarabicova, J Hrdlicka, J Neckar, M Lewis, F Kolar, T Ravingerova, MS Suleiman, A Adameova
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Slovak Research and Development Agency Medical Research Council Grant Necroptosis, a necrosis-like programmed cell death modality dependent on the activity of receptor-interacting protein kinase 3 (RIP3) and mixed lineage domain kinase domain-like pseudokinase (MLKL), plays a prominent role in mediating myocardial ischemia/reperfusion injury. However, the extent to which necroptosis contributes to such damage under short and long reperfusion has not been evaluated in detail. In Wistar rat hearts, subjected to global 30-min ischemia followed by an acute 10-min reperfusion period, with compromised cardiac function, no changes in the protein expression of the main necroptotic markers (pThr231/Ser232-RIP3, MLKL) were found. Likewise, the non-canonical pathways of necroptosis involving Ca2+/calmodulin dependent protein kinase II–mitochondrial permeability transition pore (CaMKII–mPTP) or phosphoglycerate mutase 5–dynamin-related protein 1 (PGAM5–Drp1) axes were unlikely affected by such short reperfusion. In contrast, hearts subjected to global 30-min ischemia followed by a prolonged 40-min reperfusion period exhibited worsened hemodynamic parameters what was accompanied by the increased levels of RIP3, pSer229-RIP3 and MLKL. Moreover, this reperfusion period induced MLKL translocation to the plasma membrane, indicating necroptosis execution with resultant very likely cell disruption. Similarly, activated necroptosis, evidenced by the higher levels of proteins of the canonical pathway, has been suggested to contribute to the pathogenesis of post-infarction heart failure (30-min ischemia, 42-day reperfusion). Collectively, these findings suggest that short reperfusion seems to be insufficient to induce necroptosis in the heart and the molecular mechanisms being activated during the longer reperfusion phase are needed to promote necroptotic cell dying. Therefore, inhibition of necroptosis might represent a cardioprotective strategy in the settings of chronic, but not acute myocardial ischemia/reperfusion injury.
Should we limit robot-assisted radical cystectomy with totally intracorporeal urinary diversion to neobladder patients? Head to head comparison of outcomes between robotic vs. open ileal conduit and robotic vs. open neobladder
Authors: R. Mastroianni, G. Tuderti, U. Anceschi, A.M. Bove, A. Brassetti, M. Ferriero, L. Misuraca, S. Guaglianone, M. Gallucci, G. Simone
Journal: European Urology (2022)